A cycle of hope, heartbreak

New cancer therapies do extend lives, but the drugs' effectiveness may only be temporary.

Dean Gordanier is a tax lawyer, fitness buff, father of three and, at age 54, a veteran of the roller-coaster ride of hope and despair that is becoming a way of life for growing numbers of people with cancer, thanks to the promise -- and the heartbreak -- of a new generation of cancer drugs.

Many of these drugs, which oncologists call "targeted therapies," are breathtaking, scientifically. These latest innovations, with names such as Gleevec, Avastin, Iressa, Rituxan, Herceptin and the yet-unnamed SU11248, are the closest scientists have come to the holy grail of cancer treatment -- knocking out cancer cells with great specificity but without wreaking too much havoc on the rest of the body.

Some of these drugs target specific enzymes called kinases that act as switches to control cell functions; in some cancer cells, kinases are locked in the "on" position. Others are monoclonal antibodies that attack markers on the surface of cancer cells. And some starve tumors of their blood supply by attacking proteins that make blood vessels grow.

"I am so unbelievably excited about the science because it is like standing on the Nina, the Pinta or the Santa Maria. You can see the New World coming," says Dr. George Demetri, director of the Center for Sarcoma and Bone Oncology at Boston's Dana-Farber Cancer Institute.

Gordanier is excited too, as well he might be, since these drugs have saved his life -- twice. But he is wary as well. Like any seeming miracle treatment, targeted therapies are fabulous if, and while, they work. But because cancer cells are wily and can mutate to escape a drug's action, even the most promising drug may stop working after a while.

In the fall of 1999, Gordanier went to his doctor complaining of acid indigestion. Two days after Christmas, he had tests that showed a grapefruit-sized lump in his belly. It turned out to be a potentially deadly kind of stomach cancer known as GIST (gastrointestinal stromal tumor).

In early January 2000, Gordanier signed a consent form "acknowledging that life is uncertain and evisceration has its risks," as he wryly put it in his diary, and underwent a drastic form of surgery called a "whipple" in which doctors removed the tumor, 90% of his stomach, his spleen, 70% of his pancreas and his transverse colon.

But by September, his pain -- and his cancer -- were back. Doctors tried chemoembolization, or squirting chemotherapy drugs directly into the blood supply of his tumors, which had now spread to his liver. It didn't work. In late February and early March 2001, he simply "waited to die," as he wrote in his diary.

Then he got lucky, joining a clinical trial of Gleevec for GIST. (In May 2001, the U.S. Food and Drug Administration approved Gleevec for chronic myeloid leukemia. The FDA went on to approve Gleevec for GIST in February 2002.)

"I have been saved by the bell," Gordanier wrote in his journal. "It looks like Gleevec will allow me to struggle on with a good possibility of a successful outcome, if you define success (as I do) as being able to live and work without pain and to enjoy each day as it comes and for what it brings."

But 18 months later, by December 2002, Gleevec had stopped working, as it does in about 75% of the drug's users after two years.

Once again, death loomed perilously close until Gordanier's doctor referred him to Demetri.

Demetri suggested SU11248, an experimental drug also called Sugen after the company that developed it. (It is now made by Pfizer.) Since mid-January, Gordanier has been taking SU11248. So far, it's working.

"It's a holding action," says Gordanier. "The cancers will mutate. But I will be alive as long as the doctors can keep one step ahead of the tumors."

As Gordanier and others with life-threatening illnesses have learned the hard way, it's crucial to ask questions about any new drug, even an apparent wonder drug that sounds like the best, or only, option.

"With any kind of experimental drug, you want to know two things: How likely is it to help, and what kind of harm can it cause?" says Gordanier. "If the likelihood of buying more time is low and severe side effects are a real possibility, it's hard to decide whether to risk whatever good weeks or months you have left -- no matter how desperate you are."

For instance, even when a new drug is successful by statistical standards, the impact in real life may be minimal. Avastin, for instance, garnered big headlines at the recent meeting of the American Society of Clinical Oncology because it proved an important principle: That blocking a tumor's blood supply can slow tumor growth.

But the drug only prolongs life for an average of five months in colon cancer patients. Whether that is a lot or a little "depends on what the five months are like. Is the five months likely to be spent in the intensive care unit of a hospital or at home?" asks medical ethicist Dr. Walter Robinson, a pediatric pulmonologist at Boston's Children's Hospital.